• Title/Summary/Keyword: Anti-proliferative activity

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Pro-apoptotic Effects of Platycodin D Isolated from Platycodon grandiflorum in Human Leukemia Cells (도라지 유래 사포닌 platycodin D에 의한 인체 백혈병세포의 apoptosis 유도)

  • Park, Sang Eun;Lee, Su Young;Shin, Dong Yeok;Jeong, Jin-Woo;Jin, Myung Ho;Park, Seon Young;Chung, Yoon Ho;Hwang, Hye Jin;Hong, Sang Hoon;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.3
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    • pp.389-398
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    • 2013
  • Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

Anti-cancer Effect of Hot Water Extract from Mycelium in Germanium-enriched Cordyceps militaris (게르마늄 농도를 증가 시킨 동충하초 균사체 열수 추출액의 항암효과)

  • Choi, Jeong Su;Heo, Ji Hye;Kim, Dae Jin;Namkung, Su Min;Lee, Tae Bok;Lee, Min Woo;Kim, Suhng Wook
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.2
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    • pp.69-78
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    • 2017
  • Cordyceps militaris has been used in traditional Chinese medicine owing to its anticancer and immunomodulatory activities. Germanium compounds have also been shown to be associated with many pharmacological functions, such as antimicrobial, antiviral, antitumor, antimutagenic, and immunomodulating effects. In this study, we examined the biological properties of hot water extract from mycelial liquid culture of germanium-enriched C. militaris (CMGe). CMGe displayed a concentration-dependent antiproliferation activity against four human cancer cell lines. The antiproliferative activity of CMGe was 2-4-fold lower than that of hot water extract from mycelial liquid culture in C. militaris (CM). However, CM had a concentration-dependent cytotoxicity to human bone marrow-derived mesenchymal stem cells (MSCs). Contrastingly, CMGe did not cause any cellular damage to MSCs. MSCs cultured with CMGe displayed an increased proliferative activity with no cytotoxic effect. The oral administration of CMGe inhibited increased tumor volume and weight compared with the control group. CMGe has the potential to be used as an industrial product in medicinal foods as well as in pharmaceutical products.

Modulacon of Cell Cycle Control by Histone Deacetylase Inhibitor Trichostatin A in A549 Human Non-small Cell Lung Cancer Cells (인체폐암세포 A549의 세포주기 조절인자에 미치는 histone deacetylase inhibitor trichostatin A의 영향)

  • Hwang Ji Won;Kim Young Min;Hong Su Hyun;Choi Byung Tae;Lee Won Ho;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.5 s.72
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    • pp.726-733
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    • 2005
  • Histone deacetylase (HDAC) inhibitors target key steps of tumor development. They inhibit proliferation, induce differentiation and/or apoptotic cell death, and exhibit potent antimetastatic and antiangiogenic properties in cancer cells in vitro and in vivo. Although they are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. The present study was undertaken to investiate the underlying mechanism of a HDAC inhibitor trichostatin A (TSA)-induced growth arrest and its effect on the cell cycle control gene products in a human lung carcinoma cell line A549. TSA treaoent induced the growth inhibition and morphological changes in a concentration-dependent manner. Treatment of A549 cells with TSA resulted in a concentration-dependent increased G1 (under 100 ng/ml) and/or G2/M (200 ng/ml) cell population of the cell cycle as determined by flow cytometry Moreover, 200 ng/ml TSA treatment significantly induced the population of sub-G1 cells (23.0 fold of control). This anti-proliferative effect of TSA was accompanied by a marked inhibition of cyclins, positive regulators of cell cycle progression, and cyclin-dependent kinases (Cdks) expression and concomitant induction of tumor suppressor p53 and Cdk inhibitors such as p21 and p27 Although further studies are needed, these findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of TSA in human lung carcinoma cells.

Piceatannol-Induced G1 Arrest of the Cell Cycle is Associated with Inhibition of Prostaglandin E2 Production in Human Gastric Cancer AGS Cells (Piceatannol에 의한 AGS 인체 위암세포의 G1 Arrest 및 Prostaglandin E2 생성의 억제)

  • Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.7
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    • pp.907-913
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    • 2012
  • Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

Biogenic Synthesis of Metallic Nanoparticles and Their Antibacterial Applications (금속 나노입자의 생체 합성과 항균적 적용)

  • Patil, Maheshkumar Prakash;Kim, Jong-Oh;Seo, Yong Bae;Kang, Min-jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.31 no.9
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    • pp.862-872
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    • 2021
  • Recent studies on synthesis of metallic nanomaterials such as silver (Ag), gold (Au), platinum (Pt), cerium (Ce), zinc (Zn), and copper (Cu) nanoparticles (NPs) using plants and microbes are attracted researchers for their wide range of applications in the field of biomedical sciences. The plant contains abundant of bioactive contents such as flavonoids, alkaloids, saponins, steroids tannins and nutritionals components. Similarly, microbes produce bioactive metabolites, proteins and secretes valuable chemicals such as color pigments, antibiotics, and acids. Recently reported, biogenic synthesis of NPs in non-hazardous way and are promising candidates for biomedical applications such as antibacterial, antifungal, anti-cell proliferative and anti-plasmodia activity. All those activities are dose dependent, along with their shape and size also matters on potential of NPs. Microbes and plants are great source of metabolites, those useful in biomedical field, such metabolites or chemicals involved in synthesis of NPs in an ecofriendly way. NPs synthesized using microbes or plant materials are reveals more non-toxic, facile, and cost-effective compare to chemically synthesized NPs. In present review we are focusing on NPs synthesis using biological agents such as microbes (bacteria, fungi and algae) and plant, characterization using different techniques and their antibacterial applications on pathogenic Gram-positive and Gram-negative organisms.

Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells (택란 메탄올 추출물에 의한 인체 폐암 세포주 A549의 G1 arrest 유발)

  • Park, Hyun-Jin;Jin, Soojung;Oh, You Na;Yun, Seung-Geun;Lee, Ji-Young;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.23 no.9
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    • pp.1109-1117
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    • 2013
  • Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells Lycopus lucidus, a herbaceous perennial, is used as a traditional remedy in East Asia, including China and Korea. It has been reported that L. lucidus has anti-allergic effects, inhibitory effects on cholesterol acyltransferase in high glucose-induced vascular inflammation, and anti-proliferative effects in human breast cancer cells. However, the molecular mechanisms of the anti-cancer effects of L. lucidus have not yet been fully determined. In this study, we evaluated the anti-cancer effect and the mechanism of action of L. lucidus in human lung adenocarcinoma A549 cells using methanol extracts of L. lucidus (MELL). MELL treatment showed cytotoxic activity in a dose-dependent manner and induced G1 arrest in A549 cells. The induction of G1 arrest by MELL was associated with the up-regulation of phospho-CHK2 and the down-regulation of Cdc25A phosphatase. In addition, MELL treatment induced decreased expression of G1/S transition-related proteins, including CDK2, CDK4, CDK6, cyclin D1 and cyclin E. MELL also regulated the mRNA expression of CDK2 and cyclin E. On the other hand, the expression of p53 and the cyclin-dependent kinase inhibitor p21 was not induced by MELL. Collectively, these results suggest that MELL may exert an anti-cancer effect by cell cycle arrest at G1 phase through the ATM/CHK2/Cdc25A/CDK2 pathway in A549 cells.

Effects of an Extract from the Roots of Platycodon Grandiflorum on the Levels of p53 and pRB in NCI-H460 Human Lung Carcinoma Cells (길경 수용액 추출물에 의한 NCI-H460 인체 폐암세포의 p53 및 pRB의 발현에 미치는 영향)

  • Park, Bong-Kyu;Gam, Chul-Woo;Heo, Tae-Yool;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1530-1537
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    • 2006
  • Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

Cytotoxicities of Hydrolyzed Crude Laminaran from Eisenia bicyclis on the SNU-1, HeLa and SW Cells (대황으로부터 추출한 crude laminaran 가수분해물의 암 세포독성)

  • Do, Jeong-Ryong;Kim, Dong-Soo;Park, Jong-Hyuk;Kim, Young-Myung
    • Korean Journal of Food Science and Technology
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    • v.38 no.6
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    • pp.793-798
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    • 2006
  • We investigated the effects on the cytotoxicity against several cancer cells of the hydrolysis and molecular weight fractionation of crude laminaran from E. bicyclis, a brown seaweed collected from Uleung island in Korea, was extracted with boiling water and then crude laminaran was prepared by ethanol precipitation of extract obtained after elimination of calcium alginate by calcium chloride. Crude laminaran was hydrolyzed by enzyme (Econase CE), acid (0.1 N HCl) and autoclaving ($121^{\circ}C$, 180 min), and the molecular weight fractions by ultrafiltration to generate molecular weight fractions. Total sugar and sulfate contents of hydrolyzed laminaran were 72.3 and 3.5% (enzyme hydrolysate), 68.5 and 3.0% (acid hydrolysate), 70.2 and 3.2% (autoclaved), and monosaccharides of which consisted of glucose (74.7-78.5%), mannose (9.9-11.5%), galactose (8.5-9.6%) and fucose (3.1-4.5%), respectively. When the cytotoxicity of hydrolyzed laminaran on SNU-1, HeLa and SW cells was evaluated by MTT assay, growth-inhibitory activity of the enzyme hydrolysate against cancer cells was higher than that of acid hydrolysate or autoclaved laminaran. Furthermore, the fraction at a molecular weight range of 10 to 50 kDa revealed higher anti-proliferative activities. The $IC_{50}$ values of 10-50 kDa fraction at a molecular weight range of 10 to 50 kDa revealed higher anti-proliferative activities. The $IC_{50}$ values of 10-50 kDa fractions on SNU-1, HeLa and SW cells were 60.4, 58.6 and 53.9 ${\mu}g/mL$ for enzymatic hydrolysate, 75.6, 73.5 and 77.4 ${\mu}g/mL$ for acid hydrolysate, and 61.7, 68.2 and 60.8 ${\mu}g/mL$ for autoclaved, respectively.

Curcumin Inhibits Cell Proliferation of Human Colorectal HCT116 Cells through Up-Regulation of Activating Transcription Factor 3 (ATF3) (ATF3 발현을 통한 curcumin의 대장암 세포 성장 저해)

  • Kim, Hyo-Rim;Son, Jung-Bin;Lim, Seung-Hyun;Kim, Jong-Sik
    • Journal of Life Science
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    • v.22 no.4
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    • pp.492-498
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    • 2012
  • To investigate whether phytochemicals affect cancer cell viability, human colorectal HCT116 cells were treated with four different phytochemicals. Among these phytochemicals, curcumin is the strongest inhibitor of cell proliferation. In addition, it decreased cell viability in a dose-dependent manner. To unveil the molecular mechanisms involved in the inhibition of cell proliferation by curcumin, we carried out oligo DNA microarray analysis. We found that 137 genes were up-regulated more than 2-fold, and 141 genes were down-regulated more than 2-fold by 25 ${\mu}M$ curcumin treatment. Among the up-regulated genes, we selected 3 genes (ATF-3, GADD45A, and NR4A1) to confirm microarray data. The results of RT-PCR strongly agreed with those of the microarray data. Among the phytochemicals used in this study, curcumin is the strongest inducer of ATF3 expression, and increased ATF3 expression in a dose-dependent manner. Interestingly, FACS analysis showed that the inhibition of cell growth by curcumin was recovered by ATF3-siRNA transfection. Finally, we detected the changes of gene expression by ectopic expression of ATF3. The results indicated that many up-regulated genes were related to apoptosis. Overall, these results suggest that ATF3 may play an important role in the anti-proliferative activity of curcumin in human colorectal cancer cells.

Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells (Esculetin의 caspase-3 활성을 통한 U937 인체 혈구암세포의 세포사멸 유도)

  • Park, Cheol;Hyun, Sook-Kyung;Shin, Woo-Jin;Chung, Kyung-Tae;Choi, Byung-Tae;Kwon, Hyun-Ju;Hwang, Hye-Jin;Kim, Byung-Woo;Park, Dong-Il;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.2
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    • pp.249-255
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    • 2009
  • Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.